The appearance of protein aggregates is a common pathological hallmark that is associated with Alzheimer's
disease and other major neurodegenerative disorders. Misfolded and damaged proteins that accumulate in neurodegenerative
disease can be cleared through the ubiquitin proteasome system (UPS), a highly regulated pathway whose proper
function is of paramount importance in the selective degradation of protein. Studies of the UPS have shown that alterations
in the activity of this complex system may be contributors in the etiology of specific neurodegenerative disorders.
Studies of familial genetic mutations and through experimental manipulation have suggested that a failure to clear toxic
proteins through the UPS may exert important effect on the progression of these disorders; in addition, the accumulation
of hallmark proteins themselves may in turn impair clearance by this pathway. This review will discuss recent observations
indicating that alterations in the function and efficiency of the UPS are contributors in pathogenesis of Alzheimer’s
disease, and discuss whether modulation of the UPS may be an appropriate therapeutic target in Alzheimer's disease and
similar neurological disorders.
Keywords: Neurodegenerative diseases, ubiquitin proteasome system, Alzheimer’s disease, ubiquitin, protein degradation,
amyloid, tau, ubiquitin-like proteins.
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